Organ Preservation via Immunotherapy-Based Total Neoadjuvant Therapy in Early Low Rectal Cancer (TORCH-E): A Multicenter, Open-label, Single-Arm, Phase II Study

PURPOSE: Organ preservation (OP) can be preferred in low-lying rectal cancer to reduce morbidity from radical surgery. Immunotherapy-based total neoadjuvant therapy (iTNT) showed remarkable tumor regression and facilitated OP in locally advanced rectal cancer. This study evaluated the efficacy and safety of iTNT, comprising short-course radiotherapy followed by CAPOX and toripalimab, in enabling OP for early low rectal cancer. PATIENTS AND METHODS: TORCH-E was a multicenter, single-arm phase II trial enrolling patients with T2-3bN0 rectal adenocarcinoma ≤5 cm from the anal verge. Patients received short-course radiotherapy (25 Gy/5 Fx) followed by four cycles of CAPOX plus toripalimab. Good responders were eligible for watch-and-wait (WW) or local excision (LE), and total mesorectal excision was recommended for poor responders or those with high-risk features after LE. The primary endpoint was complete response (CR), including clinical CR with WW and pathologic CR. Secondary endpoints included OP rate, adverse effects, and quality of life. RESULTS: From December 2022 to March 2024, 33 patients were enrolled, with 75.8% staged as T3. After iTNT, 16 patients achieved clinical CR and adopted WW. Pathologic CR was observed in eight of eight LE and five of nine patients who underwent total mesorectal excision. The most common grade 3 to 4 adverse event was thrombocytopenia (27.3%). After a median follow-up of 24.1 months, four local regrowths and one metastatic recurrence occurred. The total CR rate was 72.7%, and the OP rate was 60.6%. CONCLUSIONS: As an exploratory trial, TORCH-E demonstrated a promising iTNT approach achieving a high CR rate, enabling OP through WW and selective LE in early low rectal cancer, warranting subsequent randomized validation.